OncoTargets and Therapy (Aug 2020)
Exosomal-lncRNA DLEU1 Accelerates the Proliferation, Migration, and Invasion of Endometrial Carcinoma Cells by Regulating microRNA-E2F3
Abstract
Jianjun Jia,1 Suiqun Guo,2 Dong Zhang,1 Xiaohui Tian,3 Xingmei Xie1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou City, Guangdong Province 510632, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou City, Guangdong Province, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen City, Guangdong Province, People’s Republic of ChinaCorrespondence: Jianjun JiaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, No. 613, West Huangpu Avenue, Tianhe District, Guangzhou City, Guangdong Province 510632, People’s Republic of ChinaTel +86-20-38688357Email [email protected]: Long non-coding RNAs (lncRNAs) may act as oncogenes in several cancers, including endometrial carcinoma (EC). The purpose of the current study is to investigate the regulatory mechanism of exosomal-lncRNA deleted in lymphocytic leukemia1 (DLEU1) on EC.Methods: The expression levels of lncRNA DLEU1, microRNA-381-3p and E2F Transcription Factor 3 (E2F3) in EC tissues or cells were detected using quantitative reverse transcription–polymerase chain reaction (qRT-PCR). We then analysed the proliferation, migration, and invasion of EC cells by performing the MTT assay, wound healing assay, and transwell invasion assay, respectively. Identification of exosomes was detected using Western blot assay. The uptake of exosomes was detected by a confocal microscope. The effects of exosomes on EC cells were investigated by construction of cell co-culture system. The interactions among DLEU1, miR-381-3p and E2F3 were confirmed using the dual-luciferase reporter (DLR) assay.Results: LncRNA DLEU1 expression was highly up-regulated in EC tissues and cells. Knockdown of DLEU1 inhibited the proliferation, migration, and invasion of EC cells. Exosomes could be uptaken by the ambient EC cells. MiR-381-3p was a target of DLEU1 and was negatively modulated by DLEU1. Overexpression of miR-381-3p suppressed the proliferation, migration, and invasion of EC cells. Additionally, E2F3 was the target gene of miR-381-3p and was negatively modulated by miR-381-3p. Upregulation of miR-381-3p and down-regulation of E2F3 reversed the promoting effect of exosomal DLEU1 on EC cells.Conclusion: Exosomal DLEU1 accelerates the development of EC by regulating the miR-381-3p/E2F3 axis, thus DLEU1 may act as a possible therapeutic target for treating EC.Keywords: endometrial carcinoma, exosomes, lncRNA DLEU1, miR-381-3p, E2F3
